The roles of morphogenetic differentiation in controlling the phenotypic expression of neoplastic transformation, the degree of malignancy of tumors, and the susceptibility of developing organs to carcinogenesis are studied using organ culture and tissue transplantation techniques, with current emphasis on the kidney. The ability of transplacentally administered carcinogens to induce genotoxic damage in cells of embryos or fetuses exposed at different stages of gestation was determined for different species. Cells were isolated from exposed embryos and gene mutations at 3 loci were assayed in vitro with simultaneous determination of survival ability. Organ specificity of induced gene mutation is being determined in embryonal cells isolated from organs of various species exposed in utero at comparable stages of gestation. Quantitative dose curves for transplacenatally induced mutation were also obtained for selected carcinogens. Quantitative determination of transplacentally induced transformation is currently in progress. The above parameters, once completed, will be compared with in vivo transplacental tumorigenesis results.